The overall goal of the proposed R&D Program is to discover and develop unique chemotypes from marine organisms as anti-HIV agents, with novel modes of action. The specific aim of this Phase I effort is to establish and confirm several "hits 1, of unique marine chemotypes by screening approximately 20,000+ saline fermentation extracts of a diverse collection of marine microorganisms. Aphios Corporation proposes to systematically screen the its marine microorganism extract library for antiviral secondary metabolites, specifically those that will inhibit replication of the human immunodeficiency virus (HIV). Whole cell assays with strains of HIV-I and HIV-2 will be performed to detect antiviral activity. Specificity of the HIV antiviral activity will he confirmed with assays directed towards specific molecular targets like p24, reverse transcriptase, and protease. The use of proprietary SuperFluids TM extraction technology will improve the spectrum of metabolites that will be isolated. SuperFluids will also produce partially purified extracts, and enhance the probability of "clean" hits. It is anticipated that the screen will yield several new and commercially useful anti-HIV agents. Candidate anti-HIV agents, developed during the Phase I effort, will he scaled up during Phase II. The toxicity, pharmacokineties, and efficacy of the candidate compounds will also be tested. Clinical trials will he conducted in Phase III of the planned program. PROPOSED COMMERCIAL APPLICATION: Products discovered will be used for the improved treatment and prophylaxis of AIDS, leading to better survival of infected patients. The societal impact of such discoveries will be enormous.